Using bucky paper as a therapeutic aid in medical applications

ABSTRACT

Methods, systems, and uses of bucky paper are provided in the present invention. These embodiments include covering medical implants with single or multiple layers of bucky paper, treating bucky paper with various therapeutics to be released through the bucky paper to a target site, shaping bucky paper into non-conventional configurations for improved therapeutic deliver, and using bucky paper alone or in conjunction with other materials to treat a target site.

FIELD OF THE INVENTION

The present invention is directed to using bucky paper as a remedial aidin medical applications. More specifically, the present inventionregards using carbon nanotube bucky paper to facilitate acceptance of amedical implant at a target site, to facilitate healing at a target siteor to deliver therapeutic to a target site. In each case, the targetsite may be within the body of a patient or elsewhere.

BACKGROUND

Carbon nanotubes are single wall or multi-wall carbon structures withdiameters that can typically range from 1.4 nm to 15 nm and lengths thatcan range from 30 nm to 20 centimeters. Nanotubes can behave like metalsor semiconductors, can conduct electricity better than copper, cantransmit heat better than diamond, and rank among the strongestmaterials known. Bucky paper is an entangled mat of carbon nanotubes.Being made of carbon, bucky paper is bio-compatible. The carbonnanotubes that comprise the bucky paper form a highly-porous meshstructure that provides the bucky paper with moderate rigidity and highstrength.

The delivery of therapeutic via the placement of an implant at a targetsite inside a patient is an often repeated medical procedure. Thebenefits and purposes of performing such a procedure are innumerable andcan include enlarging constricted lumens, reinforcing recentlyre-enlarged lumens, replacing ruptured vessels, and targeting thedelivery of therapeutic to a specific target site. Implants used inthese procedures can be delivered through various methods and systemsincluding balloon angioplasty and catheter injection.

The vessels, lumens, and other target sites, which can be treated byimplants alone or implants in combination with therapeutics, can belocated throughout the body and can include the coronary vasculature,the esophagus, the trachea, the colon, the biliary tract, the urinarytract, the prostate, the brain, and the various other organs. Examplesof implants that have been used include: vena cava filters; stents;stent-grafts; vascular grafts; intraluminal paving systems; pace makers;venous valves; and, heart valves.

BRIEF DESCRIPTION

Methods, systems, and uses of bucky paper are provided in the variousembodiments of the present invention. These embodiments include coveringmedical implants with single or multiple layers of bucky paper, treatingbucky paper with various therapeutics to be released through the buckypaper to a target site, shaping bucky paper into non-conventionalconfigurations for improved therapeutic delivery, and using bucky paperalone or in conjunction with other materials to treat a target site.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side and enlarged view of bucky paper as may be employed invarious embodiments of the present invention.

FIG. 2 is a side and enlarged view of a stent covered with bucky paperin accord with an embodiment of the present invention.

FIG. 3 is a cross-sectional view taken along line 3-3 of FIG. 2.

FIG. 4 is side views of bucky paper shaped in the form of a tube and asack, both in accord with alternative embodiments of the presentinvention.

FIG. 5 is a side view of an implant covered with bucky paper in accordwith an alternative embodiment of the present invention.

FIG. 6 is a side view of an implant covered with bucky paper in accordwith an alternative embodiment of the present invention.

FIG. 7 is a side view of an implant covered with bucky paper in accordwith an alternative embodiment of the present invention.

FIG. 8 is a side view of an implant covered with bucky paper in accordwith an alternative embodiment of the present invention.

FIG. 9 is a side view of an implant covered with bucky paper in accordwith an alternative embodiment of the present invention.

FIG. 10 is a cross-sectional view taken along line 10-10 of FIG. 9.

FIG. 11 is a process used to cover a stent with bucky paper in accordwith an alternative embodiment of the present invention.

FIG. 12 is a cross-sectional view taken along line 12-12 of FIG. 11.

FIG. 13 is a side view of an implant covered with bucky paper in accordwith an alternative embodiment of the present invention.

FIG. 14 is a process used to cover an implant in accord with analternative embodiment of the present invention.

FIG. 15 is a process used to cover an implant in accord with analternative embodiment of the present invention.

DETAILED DESCRIPTION

Bucky paper, as used herein, includes mats or meshes of single wall,multi-wall, Y-branched, and coiled carbon nanotubes. These mats ormeshes may be manufactured through various methods and means includingthose described below. The carbon nanotubes that comprise the buckypaper may be open ended nanotubes, closed ended nanotubes, and variantsthereof.

FIG. 1 is a side view of an exemplary bucky paper 12 as may be used inaccord with the various embodiments of the present invention. In FIG. 1,the carbon nanotubes 19 of the bucky paper 12 can be clearly seen inboth the regular side view and the enlarged view provided therein. As isvisible, the numerous carbon nanotubes 19 comprising the bucky paper maybe intermingled amongst themselves and may be oriented in variouspositions. The unstructured orientation of the carbon nanotubes providesfor an irregular exterior surface of the bucky paper. The unstructuredorientation of the carbon nanotubes 19 also defines voids andinterstices throughout the bucky paper 19. These voids and intersticesvary in size and may allow materials smaller than the spaces they createto pass through the bucky paper. Moreover, while the bucky paper 19 isshown in a planar orientation, it may be formed in a curve or otherorientation as described below. The bucky paper may be made in variousshapes and sizes including polygons of uniform or varying thicknesses.By changing the thickness, shape or density of the bucky paper alone orin combination, its rigidity and flexibility may be modified.

FIG. 2 is a side and enlarged view of a stent 20 that has been coveredwith bucky paper 22 in accord with an embodiment of the presentinvention. In FIG. 2, the stent 20 is comprised of numerous stent struts21. These stent struts 21 have an outer face 23 that points outwardlyfrom the stent 20. The stent struts 21 in this embodiment have beencovered with bucky paper 22. The bucky paper 22 in this embodimentextends past both ends of the stent and covers not only the stent struts21 but also the spaces 25 between the stent struts 21. The stent 20 inthis embodiment may also be dip or spray coated with a coating prior toor after the bucky paper is adhered to the stent. Furthermore, in analternative embodiment, rather than covering the spaces 25, the buckypaper may be removed or cut away to leave open areas between the stentstruts 21. Still further, only a portion of the stent 20 or othermedical device may be covered with bucky paper.

As a result of covering the stent 20 with the bucky paper 22, when thestent 20 is placed at a target site, such as a lumen within the body,the bucky paper 22 may prevent the covered portions of the stent 20 fromcoming in direct contact with the target site. Thus, if the medicalimplant were made of metal or some other material, its adaptability tothe target site and the probability of acceptance by the target site canbe improved by covering the exposed surfaces of the implant with buckypaper.

The bucky paper 22 in this embodiment may be coupled to the stent 20 andits struts 21 through various methods and techniques. These techniques,some of which are described in greater detail below, may include,mechanically attaching the bucky paper to the stent 20 (e.g., clamping,sewing), gluing the bucky paper 22 to the stent 20, forming the buckypaper 22 around the stent 20, and directly depositing the bucky paper 22onto the stent 20. During some of these forming techniques, the buckypaper 22 will not only be positioned on the stent strut face 23 but may,also, be positioned on other surfaces of the stent strut.

The clamping technique mentioned above could include wrapping the stent20 with a layer or layers of bucky paper 22 and then using clamps toconnect the bucky paper 22 to the stent 20. These clamps could includemetallic and non-metallic wires, strands of carbon wire, and otherfasteners. Furthermore, instead of clamping the layer or layers of buckypaper 22 to the stent 20 or other medical device being wrapped by thebucky paper 22, the bucky paper 22 may also be sewn to the stent 20,another medical device or even directly onto the target site. Moreover,metallic and non-metallic wires or strands may be used to sew the buckypaper to the stent 20. Still further, glue may also be used to attachthe layer or layers of bucky paper 22 to the stent 20. Glues that may beused include cyanoacrylates, polyurethanes, and UV curable glues.

Still further, in another alternative embodiment, rather than sewing orclamping the bucky paper 22 to a medical device, it may, instead, bedirectly attached to the target site. In other words, during a medicalprocedure, the medical practitioner may directly sew or clamp one ormore layers of bucky paper 22 to the target site. This may be done toshield the target site from a medical implant that will be placed thereat a later time, as well as for various other reasons. Moreover, inanother alternative embodiment, the bucky paper may be clamped betweenthe device and the vessel wall.

As discussed in greater detail below, in various alternative embodimentsof the present invention, therapeutic may be coupled to the bucky paper,may be placed between layers of the bucky paper, and may by placedbehind the bucky paper between it and the medical device that the buckypaper covers. In so doing, therapeutic may be delivered to a target siteimmediately upon the positioning of the bucky paper at the target site,over a period of time or some combination of the two. In an alternativeembodiment, and as described below, when layers of bucky paper areclamped to the various cells of the stent 20, nanoparticles or micellaecarrying Taxol or other therapeutics may be placed between the layers ofthe bucky paper in order to deliver the Taxol or other therapeutic tothe target site.

Preferred medical devices for use in conjunction with the presentinvention include catheters, vascular catheters, balloon catheters,guide wires, balloons, filters (e.g., vena cava filters and distalprotection filters), vascular stents (including covered stents such asPTFE (polytetrafluoro-ethylene)-covered stents), stent grafts, cerebralstents, cerebral aneurysm filler coils (including GDC (Guglielmidetachable coils) and metal coils), vascular grafts, myocardial plugs,pacemakers, pacemaker leads, heart valves and intraluminal pavingsystems, filterwires, venous valves, bifurcation stents, aortic stentsand, in essence, all devices that can be utilized in the vascular systemor the prostate urinary tract bile duct.

FIG. 3 is a cross-section taken along line 3-3 of FIG. 2. As can be seenin FIG. 3, the stent 20 of FIG. 2 has struts 21 that form a circularcross-section. As can also be seen, the bucky paper 22 not only coversthese struts 21 but also spans the spaces between them. As discussedabove, while only one layer of bucky paper 22 is provided in FIG. 3,several layers may be employed. Moreover, the bucky paper 22 may also beplaced on the inside of the stent 20 as well. Still further, the stentmay also be coated with an additional coating in an alternativeembodiment. This coating may be between the bucky paper and the deviceand may be over the bucky paper and the device.

FIG. 4 provides alternative embodiments of the present invention. As canbe seen (and as mentioned above), bucky paper 42 has been formed in theshape of a cylinder 41 and the shape of a pouch 47. Accordingly, inalternative embodiments, the bucky paper 42 may be shaped in non-planarconfigurations. This may be done to adapt and contour the bucky paper tothe target site, where the bucky paper will be positioned, as well asfor other reasons. For instance, if the bucky paper 42 is formed in theshape of a sack or pouch 47, the pouch 47 may be used to surround atargeted pouch like area such as artificial bones or the heart.

The bucky paper may be used in conjunction with other materials, such assilicone rubber. For instance, the silicone rubber may be sandwichedbetween two layers of bucky paper to form a pouch, a cylinder, or otherdesired shape. If the bucky paper 42 is formed in the shape of acylinder 41, it may be implanted in a cylindrical lumen.

In these embodiments, therapeutic may be delivered to the target sitedirectly upon the placement of the bucky paper 42, over time, throughtime-release from the bucky paper 42, and by using the bucky paper 42 asa lure to alternatively delivered therapeutic. When used as a lure, thebucky paper 42 may be treated before hand by placing magnetized threadsin the paper that may then be used to attract para-magnetic orferromagnetic microparticles containing or otherwise associated withtherapeutic.

FIG. 5 is a cross-section of a wall 51 of an implant system 50 in accordwith another alternative embodiment of the present invention. In thisembodiment, the implant 50 is covered with bucky paper 52. The buckypaper 52 contains a therapeutic 53 and is in direct contact with theimplant wall 51. The therapeutics that may be used in this embodimentand others are numerous and include pharmaceutically active compounds,nucleic acids with and without carrier vectors such as lipids,compacting agents (such as histones), viruses (such as adenovirus,adenoassociated virus, retrovirus, lentivirus and a-virus), polymers,hyaluronic acid, proteins, cells and the like, with or without targetingsequences.

Other examples of therapeutic agents used in conjunction with thepresent invention include, for example, pharmaceutically activecompounds, proteins, cells, oligonucleotides, ribozymes, anti-senseoligonucleotides, DNA compacting agents, gene/vector systems (i.e., anyvehicle that allows for the uptake and expression of nucleic acids),nucleic acids (including, for example, recombinant nucleic acids; nakedDNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector orin a viral vector and which further may have attached peptide targetingsequences; antisense nucleic acid (RNA or DNA); and DNA chimeras whichinclude gene sequences and encoding for ferry proteins such as membranetranslocating sequences (“MTS”) and herpes simplex virus-1 (“VP22”)),and viral liposomes and cationic and anionic polymers and neutralpolymers that are selected from a number of types depending on thedesired application.

Non-limiting examples of virus vectors or vectors derived from viralsources include adenoviral vectors, herpes simplex vectors, papillomavectors, adeno-associated vectors, retroviral vectors, and the like.

Non-limiting examples of biologically active solutes includeanti-thrombogenic agents such as heparin, heparin derivatives,urokinase, and PPACK (dextrophenylalanine proline argininechioromethylketone); antioxidants such as probucol and retinoic acid;angiogenic and anti-angiogenic agents and factors; anti-proliferativeagents such as enoxaprin, angiopeptin, rapamycin, angiopeptin,monoclonal antibodies capable of blocking smooth muscle cellproliferation, hirudin, and acetylsalicylic acid; anti-inflammatoryagents such as dexamethasone, prednisolone, corticosterone, budesonide,estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine; calciumentry blockers such as verapamil, diltiazem and nifedipine;antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel,5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine,cisplatin, vinblastine, vincristine, epothilones, endostatin,angiostatin and thymidine kinase inhibitors; antimicrobials such astriclosan, cephalosporins, aminoglycosides, and nitrofurantoin;anesthetic agents such as lidocaine, bupivacaine, and ropivacaine;nitric oxide (NO) donors such as linsidomine, molsidomine, L-arginine,NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NOadducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, anRGD peptide-containing compound, heparin, antithrombin compounds,platelet receptor antagonists, anti-thrombin antibodies, anti-plateletreceptor antibodies, enoxaparin, hirudin, Warfarin sodium, Dicumarol,aspirin, prostaglandin inhibitors, platelet inhibitors and tickantiplatelet factors; vascular cell growth promoters such as growthfactors, growth factor receptor antagonists, transcriptional activators,and translational promoters; vascular cell growth inhibitors such asgrowth factor inhibitors, growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, antibodies recognizing receptors on endothelial progenitorcells, proteins of the tetraspanin family, such as CD9 Beta-1 and Beta-3integrins, CD63, CD81, FcgammaRll, bifunctional molecules consisting ofa growth factor and a cytotoxin, bifunctional molecules consisting of anantibody and a cytotoxin; cholesterol-lowering agents; vasodilatingagents; agents which interfere with endogenous vasoactive mechanisms;survival genes which protect against cell death, such as anti-apoptoticBcl-2 family factors and Akt kinase; and combinations thereof. Cells canbe of human origin (autologous or allogenic) or from an animal source(xenogeneic), genetically engineered if desired to deliver proteins ofinterest at the insertion site.

Polynucleotide sequences useful in practice of the invention include DNAor RNA sequences having a therapeutic effect after being taken up by acell. Examples of therapeutic polynucleotides include anti-sense DNA andRNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA toreplace defective or deficient endogenous molecules. The polynucleotidescan also code for therapeutic proteins or polypeptides. A polypeptide isunderstood to be any translation product of a polynucleotide regardlessof size, and whether glycosylated or not. Therapeutic proteins andpolypeptides include as a primary example, those proteins orpolypeptides that can compensate for defective or deficient species inan animal, or those that act through toxic effects to limit or removeharmful cells from the body. In addition, the polypeptides or proteinsthat can be injected, or whose DNA can be incorporated, include withoutlimitation, angiogenic factors and other molecules competent to induceangiogenesis, including acidic and basic fibroblast growth factors,vascular endothelial growth factor, hif-1, epidermal growth factor,transforming growth factor α and β, platelet-derived endothelial growthfactor, platelet-derived growth factor, tumor necrosis factor α,hepatocyte growth factor and insulin like growth factor; growth factors;cell cycle inhibitors including CDK inhibitors; anti-restenosis agents,including p15, p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2Fdecoys, thymidine kinase (“TK”) and combinations thereof and otheragents useful for interfering with cell proliferation, including agentsfor treating malignancies; and combinations thereof. Still other usefulfactors, which can be provided as polypeptides or as DNA encoding thesepolypeptides, include monocyte chemoattractant protein (“MCP-1”), andthe family of bone morphogenic proteins (“BMP's”). The known proteinsinclude BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8,BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16.Currently preferred BMP's are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6and BMP-7. These dimeric proteins can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively or, in addition, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNA's encodingthem.

Bucky paper is a hydrophobic substance. Consequently, when hydrophobicagents, such as placitaxel, are used as therapeutics, a simple solutionto treat the bucky paper with the therapeutic would be to dip the buckypaper (and the device, if the bucky paper is coupled to a medicaldevice) in a solution containing the therapeutic agent. Now carried bythe bucky paper, the therapeutic may be partially or completely releasedfrom it when the bucky paper is positioned at a target site.

Comparatively, when hydrophylic therapeutics are used, they may first beencapsulated in liposomes or polysaccharides that are subsequentlyembedded into the bucky paper. Alternatively, the hydronhilictherapeutics may be crystallized or frozen and then placed within thebucky paper. Still further, microtubes, loaded with therapeutics, mayalso be embedded in the bucky paper for subsequent release and delivery.

FIG. 6 is a side cross-section of an implant system 60 in accord withanother alternative embodiment of the present invention. In theembodiment of FIG. 6 an implant 61 is covered with a first layer ofbucky paper 62, a therapeutic carrier 64, and a second layer of buckypaper 65. The therapeutic carrier 64 in this embodiment contains atherapeutic 63. The therapeutic coating or carrier 64 may be used toregulate the release of the therapeutic 63 from the implant system, andto prevent or reduce the burst phenomenon associated with therapeuticdelivery. It may also be used to adhere the second layer of bucky paper65 on the implant 61. Furthermore, if the therapeutic is a biologicallyactive material, it may be permanently resident within the carrier 64and not released by the carrier.

This implant system 60 may be manufactured by assembling the layersdirectly on the medical device. These layers may also be assembledelsewhere and then transferred onto the implant already layeredtogether. Alternatively, the two bucky paper layers may be placed on themedical implant 61 with the carrier 64 and therapeutic 63 being injectedinto the space between them at a later time.

FIG. 7 is a side view of an alternative embodiment of the presentinvention. In FIG. 7, the implant system 70 includes an implant 71, atherapeutic coating 74 positioned on top of the implant 71, and buckypaper 72 positioned on top of the therapeutic coating 74. Here, thetherapeutic coating 74 is positioned directly on top of the implant 71.

Coatings used with the present invention may comprise various polymericmaterial/drug agent matrices, i.e. gel/drug combinations. These may beformed, for example, by admixing a drug agent with a liquid polymer, inthe absence of a solvent, to form a liquid polymer/drug agent mixture.Curing of the mixture in these embodiments may occur in-situ. Tofacilitate curing, a cross-linking or curing agent may be added to themixture prior to application thereof. Addition of the cross-linking orcuring agent to the polymer/drug agent liquid mixture must not occur toofar in advance of the application of the mixture in order to avoidover-curing of the mixture prior to application thereof. Curing may alsooccur in-situ by exposing the polymer/drug agent mixture, afterapplication to the luminal surface, to radiation, such as ultravioletradiation or laser light, heat, or by contact with metabolic fluids suchas water at the site where the mixture has been applied to the luminalsurface. In coating systems employed in conjunction with the presentinvention, the polymeric material may be either bioabsorbable orbiostable. The polymers described herein, which may be formulated as aliquid, may be used to form the polymer/drug agent mixture.

In a preferred embodiment, the polymer used to coat the medical devicemay be provided in the form of a coating on an expandable portion of themedical device. After applying the drug solution to the polymer andevaporating the volatile solvent from the polymer, the medical device,covered by the polymer and bucky paper, may be inserted into a bodylumen and positioned at a target location. In the case of a ballooncatheter, the expandable portion of the catheter may be subsequentlyexpanded to bring the drug-impregnated implant system into contact withthe lumen wall. The therapeutic may then be released from the polymer asthe polymer slowly dissolves in the aqueous bodily fluids or as thetherapeutic diffuses out of the polymer. This enables administration ofthe drug to be site-specific, limiting the exposure of the rest of thebody to the therapeutic.

The stent used in the present invention for the coatings or carriers ispreferably capable of absorbing a substantial amount of therapeuticsolution. When applied as a coating on a medical device in accord withthe present invention, the dry polymer is typically on the order of fromabout 1 to about 50 microns thick. In the case of a balloon catheter,the thickness is preferably about 1 to 10 microns thick, and morepreferably about 2 to 5 microns. Very thin polymer coatings, e.g., ofabout 0.2-0.3 microns and much thicker coatings, e.g., more than 10microns, are also possible. It is also within the scope of the presentinvention to apply multiple layers of polymer coating in addition tomultiple layers of bucky paper onto a medical device. Such multiplelayers may be the same or different polymer materials. Furthermore,using polyelectrolytes (layer by layer compositions) the polymer layerthickness may be reduced by encapsulating the therapeutic agent inbetween the polymer layers. These layers may be on the order of 5-50nanometers.

The carriers and coatings used in the present invention may behydrophilic or hydrophobic, and may be selected from the groupconsisting of polycarboxylic acids, cellulosic polymers, includingcellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone,cross-linked polyvinylpyrrolidone, polyanhydrides including maleicanhydride polymers, polyamides, polyvinyl alcohols, copolymers of vinylmonomers such as EVA, polyvinyl ethers, polyvinyl aromatics,polyethylene oxides, glycosaminoglycans, polysaccharides, polyestersincluding polyethylene terephthalate, polyacrylamides, polyethers,polyether sulfone, polycarbonate, polyalkylenes including polypropylene,polyethylene and high molecular weight polyethylene, halogenatedpolyalkylenes including polytetrafluoroethylene, polyurethanes,polyorthoesters, proteins, polypeptides, silicones, siloxane polymers,polylactic acid, polyglycolic acid, polycaprolactone,polyhydroxybutyrate valerate and blends and copolymers thereof as wellas other biodegradable, bioabsorbable, and biostable polymers andcopolymers. Coatings from polymer dispersions such as polyurethanedispersions (BAYHYDROL®, etc.) and acrylic latex dispersions are alsowithin the scope of the present invention. The polymer may be a proteinpolymer, fibrin, collagen and derivatives thereof, polysaccharides suchas celluloses, starches, dextrans, alginates and derivatives of thesepolysaccharides, an extracellular matrix component, hyaluronic acid, oranother biologic agent or a suitable mixture of any of these, forexample. In one embodiment of the invention, the preferred polymer ispolyacrylic acid, available as HYDROPLUS® (Boston ScientificCorporation, Natick, Mass.), and described in U.S. Pat. No. 5,091,205.U.S. Pat No. 5,091,205 describes medical devices coated with one or morepolyisocyanates such that the devices become instantly lubricious whenexposed to body fluids. In another preferred embodiment of theinvention, the polymer is a copolymer of polylactic acid andpolycaprolactone.

FIG. 8 is a cross-section of another alternative embodiment of thepresent invention. The implant system 80 of FIG. 8 contains an implant81, therapeutic coating 84, a delivery barrier 85, and PB anchors 86.The barrier may be made from a biodegradable layer like poly vinylalcohol or PLLA or a polysaccharide or another multi-layerpolyelectrolyte composition. It could also be made from a stable porouspolymer like a polyurethane or SIBS. The PE anchors 86 may be formeddirectly into the bucky paper 82 and may protrude from it. The PEanchors 86 may be used, as is shown in FIG. 8, to secure the bucky paper82, through the therapeutic coating 84, to the medical implant 81. Thissecurement may be done by melting the PE anchors. In addition to usingthe coating 84 to control the release of therapeutic from the implantsystem 81, the delivery barrier 85 may also be used to perform thisfunction. This delivery barrier 85 may be comprised of materials thataffect the delivery of the therapeutic in the coating 84. Alternatively,the barrier 85 may simply dissolve over time, thereby providing for therelease of therapeutic from the medical implant once the barrierdissolves. The PB anchors 86 formed in the bucky paper 82 of thisembodiment may also be used, in alternative embodiments, to attach thebucky paper 82 directly to the target site or to other bucky paper inorder to form layers of bucky paper. the bucky paper 82 of thisembodiment may also be used, in alternative embodiments, to attach thebucky paper 82 directly to the target site or to other bucky paper inorder to form layers of bucky paper.

In another alternative embodiment of the present invention, the implantsystem 80 may contain an implant 81 with a therapeutic coating within acarrier layer (e.g., styrene-isobutylene-styrene) and a barrier layer,wherein the barrier layer may be bucky paper. The barrier layer may befurther improved by associating it with endothelial growth stimulatingsubstances like Heparin as described below.

FIG. 9 is an alternative embodiment of the present invention. In FIG. 9,the implant system 90 includes layers of bucky paper 92 positioned onthe inside and outside surfaces of the implant strut 91. These layers ofbucky paper 92 are positioned on top of therapeutic layers 94. In thisembodiment, the outer most bucky paper layer may be untreated while theinner layer of bucky paper may be treated. This treatment can include aplasma process to create chemical anchors such as hydrophilic andcarboxylic groups to which one can attach therapeutics.

FIG. 10 is a cross-section along line 10-10 of FIG. 9. As can be seen inFIG. 10, the layers of bucky paper 92 and the therapeutic carrier 94 donot cover all sides of the implant strut 91. Rather, the bucky paper 92and the therapeutic carrier cover the inside and outside facing surfacesof the strut 91. In alternative embodiments, the bucky paper and thecarrier may, instead, cover the entire surface of the implant's struts.

FIG. 11 is an alternative embodiment of the present invention regardingthe placement of bucky paper around a medical implant. In thisembodiment rolled bucky paper 112 is inserted into a stent 111 (step 1)and then folded back over the stent 111 (step 2) in order to cover thestent 111 with the bucky paper 112. The covered stent 111 is shown instep 3. Also visible in step 3 is the fold line 118, the stent 111, andthe bucky paper 112. Alternatively, the paper may first be folded androlled only once, without an overlap, the stent being placed in thespace between.

FIG. 12 is a cross-section taken along line 12-12 of FIG. 11. The buckypaper 112 can be clearly seen on both the inside and the outside surfaceof the stent 111. The internal passage 121, which is formed by the innersurfaces of the bucky paper 112, can also be seen in this sectionalview.

FIG. 13 is a sectional view of an implant system 130 in accord with analternative embodiment of the present invention. In this embodiment, arelease control coating 138 has been placed on top of the bucky paper132, which is in turn positioned on top of a therapeutic carrier 134.This carrier 134 may include microtubes, ceramic nano-particles, andliposome microparticles. Furthermore, the therapeutic may beencapsulated in biodegradable nano- or microparticles by usingpoly-electrolyte multilayers. These particles may be designed to open upupon exposure to different phs, changes in osmotic pressure, and changesin external pressure, heat or light.

Bucky paper may be manufactured in one embodiment from commerciallyobtained SWNT suspensions (Triton X-100 or toluene solution) that havebeen vacuum filtered to allow for free standing films of highlyentangled nanotube ropes. In one embodiment, the bucky paper may be madeby vacuum filtering approximately 4 g of approximately 0.6 mg/ml ofpreviously diluted (˜80 ml de-ionized H₂O) nanotube solution. The filtermay be a (Millipore LS, 47 mm in diameter or Whatman Anodisc 47 filter20 mm pore site) polytetrafluoroethylene filter.

Once created, the filtered mat may then be washed with 200 ml ofde-ionized water and 100 ml of methanol. A drying vacuum and heat (70°C.) may be applied for 12 hours. These steps were found to produce buckypaper having a thickness ranging from 13-33 nanometers and a density of0.3 to 0.4 g/cm³.

These nanotubes may be chemically modified by reacting them withsulfuric and nitric acid. Moreover, hydrophylic and carboxylic groupsmay be created on the surface of the nanotubes and may be used to bindheparin and albumin molecules to the surface of the nanotubes, which maypromote endothelial cell seeding. Plasma may also be used to change theproperties of the nanotubes in order to couple various biologicallyactive molecules to them. When these modified nanotubes have beencreated they may be mixed with untreated nanotubes.

FIG. 14 regards a process that may be used in accord with anotheralternative embodiment of the present invention. In FIG. 14, a containerof single wall nanotubes in solution 1401 is poured onto an implant 141that has been placed on top of a filter 1403. The filter 1403 is sizedto allow the suspending solution to pass through it but to trap the SWNTon top of it. As a result, bucky paper is formed on top of the filter1403 and on top of the implant 141.

Alternatively, rather than form the bucky paper on a flat filtersurface, it may be formed on a cylindrical or tubular filter. Suction orcentrifugal forces may be used to create the bucky paper on the filteror to facilitate its drying. Still further, as described above, thefilter may be formed in the shape of a bag in order to form the pouchshaped bucky papers described above. Moreover, once the bucky paper isconfigured, an implant may be placed adjacent to it and additional buckypaper may be formed on top of it to completely encircle the implant.

FIG. 15 is a manufacturing process that may be used to manufactureimplant systems in accord with another alternative embodiment of thepresent invention. In the embodiment of FIG. 15, a solution containingSWNT 152 may be sprayed onto an implant 151. After spraying, the SWNTs152 that remain on the implant, once the carrier (toluene) is flashedoff, may be condensed or compacted onto the implant by applying acompressive force to the SWNT 152. This compressive force may be appliedby a shrink tube or any other suitable means. The compressive forceapplied to the SWNT 152 is shown in FIG. 15 by arrows 156.

While various embodiments of the present invention have been described,other embodiments are also plausible. For instance, the implant may benotched or grooved such that therapeutic may be placed therein. Thesegrooves or notches may then be covered with the bucky paper, therebycovering individual vats or channels of therapeutic. Moreover, asdiscussed above with regard to FIG. 2, the bucky paper may not onlycover a device but may also extend past either or both ends of thedevice.

1. A medical implant system comprising: a medical implant having anexterior surface; and a first layer of bucky paper covering at least aportion of the exterior surface.
 2. The medical implant system of claim1 wherein the first layer of bucky paper covers the entire exteriorsurface of the medical implant and the bucky paper contains carbonnanotubes with carboxylic groups positioned on a surface of the carbonnanotubes.
 3. The medical implant system of claim 1 wherein the medicalimplant has a non-continuous exterior surface forming spaces betweenexterior elements of the medical implant and wherein portions of thefirst layer of bucky paper have been removed over areas coinciding withat least one space between the exterior elements of the medical implant.4. The medical implant system of claim 1 wherein the medical implant isa stent.
 5. The medical implant system of claim 1 further comprising: atherapeutic carried by the first layer of bucky paper.
 6. The medicalimplant system of claim 1 wherein therapeutic is positioned between thefirst layer of bucky paper and the medical implant.
 7. The medicalimplant system of claim 1 further comprising a polymer layer disposedbetween the first layer of bucky paper and the medical implant, whereintherapeutic is positioned within the polymer layer.
 8. The medicalimplant system of claim 1 wherein therapeutic is placed in a carrier,the carrier positioned in the first layer of bucky paper.
 9. The medicalimplant system of claim 1 further comprising: a second layer of buckypaper covering at least a portion of the medical implant.
 10. Themedical implant system of claim 9 further comprising: a therapeuticpositioned between the layers of bucky paper.
 11. The medical implantsystem of claim 10 wherein the therapeutic is contained within apolymer.
 12. The medical implant system of claim 1 further comprising: atherapeutic, the therapeutic carried by the first layer of bucky paper,the therapeutic being in a crystallized state.
 13. The medical implantsystem of claim 1 wherein the bucky paper contains magnetically chargedparticles.
 14. The medical implant system of claim 1 wherein the buckypaper contains anchors extending from the exterior surface, the anchorscoupling the first layer of bucky paper to the implant.
 15. The medicalimplant system of claim 9 wherein the first layer of bucky papercontains a first therapeutic and the second layer of bucky papercontains a second therapeutic.
 16. The medical implant system of claim 5wherein the therapeutic is within a carrier.
 17. The medical implantsystem of claim 1 further comprising: a therapeutic release barriercovering the first layer of bucky paper and a therapeutic.
 18. Themedical implant system of claim 1 wherein the first layer of bucky papervaries in thickness.